Ruminal fermentation characteristics and related feeding values of compound feeds and their constituting single feeds studied by using in vitro techniques.

Single concentrate feeds are mixed together forming compound feeds for cattle. However, knowledge regarding the potential interactions (associative effects) between the feeding values of single feeds in compound feeds is lacking. The main objective of the present study was to evaluate ruminal fermentation characteristics and feeding values of eight industrially produced compound feeds in mash form from their constituent single feeds for dairy cows through in vitro assays. Additivity was given for gas production (GP), digestibility of organic matter (dOM) and utilisable CP at the duodenum (uCP). Additivity of CP fractions (determined using the Cornell Net Carbohydrate and Protein System (CNCPS)) was dependent on the fraction and compound feed type; however, the effective degradation calculated from CP fractions (EDCNCPS) showed additivity. Additivity was not given for intestinal digestibility of rumen-undegraded protein (IDRUP) for five out of eight compound feeds. Precise calculation of metabolisable energy (ME) of compound feeds from ME of single feeds was possible when using the same ME equations for all single and compound feeds. Compound feeds are often provided in pellet form; therefore, our second objective was to evaluate the effects of pelleting on ruminal fermentation characteristics and feeding values of compound feeds. Pelleting affected GP at 24 h (GP24; up to 2.4 ml/200 mg DM), dOM (up to 2.3 percentage point (pp)) and ME (up to 0.3 MJ/kg DM), but these differences were overall small. More considerable effects of pelleting were observed for uCP, which was increased in all compound feeds except the two with the highest CP concentrations. The IDRUP was lower in most compound feeds following pelleting (up to 15 pp). Pelleting also affected CP fractions in a non-systematic way. Overall, the effects of pelleting were not considerable, which could be because pelleting conditions were mild. Our third objective was to compare in situ ruminal CP degradation (EDIN_SITU) of compound feeds with ED using two prediction methods based on CP fractions. EDIN_SITU reference data were obtained from a companion study using the same feeds. Prediction accuracy of EDIN_SITU and EDCNCPS was variable and depended on the compound feed and prediction method. However, future studies are needed as to date not enough data are published to draw overall conclusions for the prediction of EDIN_SITU from CP fractions.

Determination of in situ ruminal degradation of phytate phosphorus from single and compound feeds in dairy cows using chemical analysis and near-infrared spectroscopy.

The ruminal degradation of P bound in phytate (InsP6) can vary between feeds, but data on ruminal degradation of InsP6 from different feedstuffs for cattle are rare. One objective of this study was to increase the data base on ruminal effective degradation of InsP6 (InsP6ED) and to assess if InsP6ED of compound feeds (CF) can be calculated from comprising single feeds. As a second objective, use of near-infrared spectroscopy (NIRS) to predict InsP6 concentrations was tested. Nine single feeds (maize, wheat, barley, faba beans, soybeans, soybean meal (SBM), rapeseed meal (RSM), sunflower meal (SFM), dried distillers' grains with solubles (DDGS)) and two CF (CF1/CF2), consisting of different amounts of the examined single feeds, were incubated for 2, 4, 8, 16, 24, 48 and 72 h in the rumen of three ruminally fistulated Jersey cows. Samples of CF were examined before (CF1/CF2 Mash) and after pelleting (CF1/CF2 Pellet), and InsP6ED was calculated for all feeds at two passage rates (InsP6ED5: k = 5%/h; InsP6ED8: k = 8%/h). For CF1 and CF2, InsP6ED was also calculated from values of the respective single feeds. Near-infrared spectra were recorded in duplicate and used to establish calibrations to predict InsP6 concentration. Besides a global calibration, also local calibrations were evaluated by separating samples into different data sets based on their origin. The InsP6ED8 was highest for faba beans (91%), followed by maize (90%), DDGS (89%), soybeans (85%), wheat (76%) and barley (74%). Lower values were determined for oilseed meals (48% RSM, 65% SFM, 66% SBM). Calculating InsP6ED of CF from values of single feeds underestimated observed values up to 11 percentage points. The NIRS calibrations in general showed a good performance, but statistical key data suggest that local calibrations should be established. The wide variation of InsP6ED between feeds indicates that the ruminal availability of P bound in InsP6 should be evaluated individually for feeds. This requires further in situ studies with high amounts of samples for InsP6 analysis. Near-infrared spectroscopy has the potential to simplify the analytical step of InsP6 in the future, but the calibrations need to be expanded.

Prececal amino acid digestibility and phytate degradation in broiler chickens when using different oilseed meals, phytase and protease supplements in the feed.

The purpose of this study was to investigate the effects of phytase and protease supplementation on prececal (pc) amino acid (AA) digestibility, phytate (InsP6) degradation, and MEn concentration in diets using 3 oilseed meals as main protein sources in broiler chicken feed. The broiler chicken diets, which lacked mineral phosphorus, contained either soybean meal (SBM), SBM and rapeseed meal (SBM/RSM), or SBM and sunflower meal (SBM/SFM) as main protein sources. Diets were not supplemented with enzymes or supplemented with 1,500 or 3,000 FTU phytase/kg, or with 1,600 mg protease/kg. For diets containing SBM as the main protein source, the effects of phytase supplementation with and without monocalcium phosphate were also investigated. Data were obtained during 2 subsequent runs from days 14 to 22 and from days 23 to 31. Each diet was tested using 8 replicates with 4 replicates per run. For pc AA digestibility, no significant interactions were observed between main protein sources, enzyme supplementation, or addition of monocalcium phosphate except for Cys. Supplementation of 1,500 FTU phytase/kg increased pc digestibility of all AA. No differences in pc AA digestibility were observed between 1,500 and 3,000 FTU phytase/kg supplementation treatments. Prececal disappearance of InsP6 and pc P digestibility were greater in the high phytase supplementation treatment. Protease supplementation increased pc digestibility of all AA except for Cys when SBM/RSM was the main protein source. Supplementation of protease and 3,000 FTU phytase/kg increased MEn concentrations. The effect of phytase on pc AA digestibility was fully expressed at a lower supplementation level than needed for a maximized pc InsP6 disappearance and MEn concentration.

Variation of lupin protein degradation in ruminants studied in situ and using chemical protein fractions.

The main objective of this study was to evaluate the variability in in situ CP degradation characteristics of 15 batches lupin grains from nine genotypes in a standardised approach. This study also investigated whether differences in CP degradation can be described by protein fractionation using the Cornell Net Carbohydrate and Protein System (CNCPS) and also whether thermal processing of lupins has an effect on CP degradation in the rumen and analysed protein fractions. The rising political and consumer demand for milk products from dairy production systems based on domestic protein sources and the wide range of lupin types and varieties that can be chosen as protein feed in dairy nutrition requires research to determine the variability in CP degradation characteristics in the rumen. For CP degradation measurements, ground grains were incubated in the rumen of three lactating Jersey cows fitted with a ruminal cannula for different times from 2 to 48 h, and the washing loss of non-incubated samples was also measured. Protein fractions were analysed according to CNCPS and used for the estimation of ruminally degraded protein. In situ CP degradation parameters varied widely between untreated samples. The mean value for the washout fraction was 29.3% (from 16.4% to 43.6%). The potentially degradable fraction averaged 70.5% (from 55.6% to 83.7%), hence maximal degradation of CP was close to completeness. Mean degradation rate was 16.6%/h (from 12.6 to 21.0%/h). Variation in estimated parameters led to variation in the effective degradation (ED) averaging 76.6% (from 67.3% to 83.0%) when calculated assuming a ruminal outflow of 8%/h. Thermal treatment of lupins induced changes in degradation characteristics, primarily by lowering degradation rates, and also led to a significant reduction in ED. The ED calculated from analysed protein fractions averaged 10 percentage points higher than ED calculated from in situ parameters for untreated grains. The ED based on protein fractionation was also reduced by heat treatment, but the correlation with in situ based ED was poor. It can be concluded that the variation in ED indicates a potential to increase the amount of rumen undegraded protein without additional chemical or physical treatment and the effect of genetic factors and agronomic practices on ED of lupin grains should be investigated in systematic studies in the future.

Prediction of CP and starch concentrations in ruminal in situ studies and ruminal degradation of cereal grains using NIRS.

Ruminal in situ incubations are widely used to assess the nutritional value of feedstuffs for ruminants. In in situ methods, feed samples are ruminally incubated in indigestible bags over a predefined timespan and the disappearance of nutrients from the bags is recorded. To describe the degradation of specific nutrients, information on the concentration of feed samples and undegraded feed after in situ incubation ('bag residues') is needed. For cereal and pea grains, CP and starch (ST) analyses are of interest. The numerous analyses of residues following ruminal incubation contribute greatly to the substantial investments in labour and money, and faster methods would be beneficial. Therefore, calibrations were developed to estimate CP and ST concentrations in grains and bag residues following in situ incubations by using their near-infrared spectra recorded from 680 to 2500 nm. The samples comprised rye, triticale, barley, wheat, and maize grains (20 genotypes each), and 15 durum wheat and 13 pea grains. In addition, residues after ruminal incubation were included (at least from four samples per species for various incubation times). To establish CP and ST calibrations, 620 and 610 samples (grains and bag residues after incubation, respectively) were chemically analysed for their CP and ST concentration. Calibrations using wavelengths from 1250 to 2450 nm and the first derivative of the spectra produced the best results (R 2 Validation=0.99 for CP and ST; standard error of prediction=0.47 and 2.10% DM for CP and ST, respectively). Hence, CP and ST concentration in cereal grains and peas and their bag residues could be predicted with high precision by NIRS for use in in situ studies. No differences were found between the effective ruminal degradation calculated from NIRS estimations and those calculated from chemical analyses (P>0.70). Calibrations were also calculated to predict ruminal degradation kinetics of cereal grains from the spectra of ground grains. Estimation of the effective ruminal degradation of CP and ST from the near-infrared spectra of cereal grains showed promising results (R 2>0.90), but the database needs to be extended to obtain more stable calibrations for routine use.

In situ and in vitro evaluation of crude protein degradation and utilisable crude protein content of barley, rye and triticale grains for ruminants.

Rations for dairy cows are comprised of high proportions of cereal grains. Thus, despite their low crude protein (CP) content, grains can contribute considerably to the CP intake of dairy cows. This study was conducted to describe and compare ruminal CP degradation of a broad range of barley, rye and triticale genotypes in situ and in vitro and different methods to estimate the utilisable CP at the duodenum (uCP). Twenty samples each of rye, barley and triticale were incubated in situ and in vitro. Exponential regression analyses were used to estimate in situ degradation parameters. Further, the effective degradability (ED), ruminal undegraded CP (UDP) and uCP for ruminal passage rates of 5% and 8% per hr were estimated. The uCP was estimated in vitro and based on two different approaches using in situ UDP data and estimates of microbial synthesised protein (based on fermented organic matter [fOM] or equations of the Gesellschaft für Ernährungsphysiologie). The degradation rate declined from rye (43% per hr) to triticale (27% per hr) to barley (20% per hr), and it exhibited remarkable variation between the genotypes of a single species. The maximal degradable CP fraction also differed between the species, but was overall very high (94%-99%). The lowest washout fraction (26%) and the highest variation in ED (77%-86% and 69%-80% for a passage rate of 5% and 8% per hr, respectively) were found in barley. The in situ uCP content (estimated using fOM) was lower for barley than for rye and triticale at ruminal passage rates of 5% and 8% per hr (barley: 157 g/kg DM at both passage rates; rye and triticale: 168 (at 5% per hr) and 169 (at 8% per hr) g/kg DM). In vitro estimations of uCP did not differ between the grain species and uCP estimated according to GfE was higher for triticale than for barley and rye, which did not differ. The low variation within a single grain species and the weak correlations between ruminal CP degradation and nutrient concentrations suggested that differentiation of ED and uCP between the genotypes of a single grain species is not necessary.

In situ and in vitro ruminal starch degradation of grains from different rye, triticale and barley genotypes.

In recent years, advances in plant breeding were achieved, which potentially led to modified nutritional values of cereal grains. The present study was conducted in order to obtain a broad overview of ruminal digestion kinetics of rye, triticale and barley grains, and to highlight differences between the grain species. In total, 20 genotypes of each grain species were investigated using in situ and in vitro methods. Samples were ground (2 mm), weighed into polyester bags, and incubated in situ 1 to 48 h in three ruminally cannulated lactating dairy cows. The in vitro gas production of ground samples (1 mm) was measured according to the 'Hohenheim Gas Test', and cumulative gas production was recorded over different time spans for up to 72 h. There were significant differences (P<0.05) between the species for most parameters used to describe the in situ degradation of starch (ST) and dry matter (DM). The in situ degradation rate (c) and effective degradability (assuming a passage rate of 8%/h; ED8) of ST differed significantly between all grains and was highest for rye (rye: 116.5%/h and 96.2%; triticale: 85.1%/h and 95.0%; barley: 36.2%/h and 90.0% for c and ED8, respectively). With respect to DM degradation, the ranking of the species was similar, and predicted c values exhibited the highest variation within species. The in vitro gas production rate was significantly higher (P<0.05) for rye than for triticale and barley (rye: 12.5%/h; triticale: 11.5%/h; barley: 11.1%/h). A positive relationship between the potential gas production in vitro and the maximal degradable DM fraction in situ was found using all samples (r=0.84; P<0.001) as well as rye (P=0.002) and barley (P<0.001) alone, but not for triticale. Variation in ruminal in situ degradation parameters within the grain species resulted from the high c values, but was not reflected in the ED estimates. Therefore, the usage of mean values for the ED of DM and ST for each species appears reasonable. Estimated metabolisable energy concentrations (ME, MJ/kg DM) and the estimated digestibility of organic matter (dOM, %) were significantly lower (P<0.05) for barley than for rye and triticale. Rye and triticale dOM and ME values were not significantly different (P=0.386 and 0.485).

No effects of hydrocortisone and dexamethasone on pain sensitivity in healthy individuals.

BACKGROUND: There is some evidence that stress-induced cortisol increase leads to a decrease in pain, while lowering cortisol levels enhances pain sensitivity, but no study has yet investigated both pharmacological enhancement and reduction of cortisol levels in the same individuals. METHODS: Firstly, we tested in 16 healthy individuals whether the treatment with hydrocortisone and dexamethasone, respectively, results in altered pain thresholds. Secondly, we aimed to test whether hormone effects are different across the pain range by using ratings for pain stimuli with varying intensity; and thirdly, we tested whether cortisol levels influence the discrimination ability for painful stimuli. RESULTS: Despite substantial effects of dexamethasone and hydrocortisone administration on cortisol levels, no effect of these drugs was seen in terms of pain sensitivity (pain threshold, pain rating, pain discrimination ability), although comprehensively examined. However, in the placebo condition, a significant negative correlation between cortisol and pain thresholds was seen. Similarly, there were also strong negative associations between cortisol levels in the placebo condition and pain thresholds after drug treatment (especially after hydrocortisone). CONCLUSION: These findings suggest that short-term variations of cortisol do not influence pain sensitivity whereas, in general, high levels of cortisol are associated with increased pain sensitivity, at least for weak to moderate stimuli.

Low in vitro third-body wear on total hip prostheses induced by calcium sulphate used for local antibiotic therapy.

In case of implant associated infection, implant preservation is associated with high failure rates. Therefore, a removal or exchange of the implant is most often mandatory for treatment success. Alternatively, under certain conditions, local antibiotic delivery can be applied - preserving the implant, using for example calcium sulphate as a resorbable carrier. In this work, third-body wear on total hip prostheses caused by calcium sulphate particles was tested in a hip simulator. Inlays made of ultra-high-molecular-weight polyethylene (UHMWPE) and cross-linked polyethylene (XLPE) against 28 mm CoCrMo heads and 36 mm alumina pairings were tested in triplicate, both with and without calcium sulphate particles in the test liquid. Neither the alumina articulations nor the CoCrMo heads were affected by the calcium sulphate particles since calcium sulphate is a relatively soft material. The polyethylene inlays showed 39-89 % higher wear during exposure compared to references, but wear returned to normal when no more particles were added. Thus, calcium sulphate might be used as antibiotic carrier even in the presence of total hip prostheses without fearing excessive third-body wear.

[Cardiac computed tomography and ablation of atrial fibrillation]. / Kardiales CT und Ablation von Vorhofflimmern.

Both cardiac computed tomography (CT) and interventional electrophysiology (EP) have evolved considerably in recent years. Technical improvements in CT have significantly reduced the radiation dose in cardiac applications. This imaging technology plays an important role in preprocedural planning and guidance of the procedures in many EP centers worldwide. Furthermore, CT is the imaging modality of choice to diagnose relevant complications in ablation of atrial fibrillation, e.g. pulmonary vein stenosis or atrioesophageal fistula. In anatomically driven ablation procedures, such as balloon-based procedures in atrial fibrillation, detailed analysis of the relevant cardiac structures is absolutely crucial not only to reduce radiation exposure and procedure times but also to improve ablation success and to reduce the occurrence of complications. Current software applications enable 3-dimensional reconstruction of cardiac images and the integration into electroanatomical navigation systems. This article reviews the available evidence in this field and highlights recent developments in image guidance for ablation of atrial fibrillation.

Cryoballoon in atrial fibrillation ablation.

Encouraging results of ablation therapy in patients with paroxysmal atrial fibrillation (AF) have prompted changes in professional practice guidelines. The most recent European guidelines have suggested that ablation might be offered as first-line therapy in selected patients. Cryoballoon ablation is a promising technology in interventional AF therapy. Two different sizes of the cryoballoon are currently available: a smaller (23 mm) and a larger (28 mm) balloon relative to the ostial diameter of the pulmonary veins. New tools, the circular mapping catheter and the use of intracardiac echocardiography, provide important periprocedural information. A meta-analysis of previous studies revealed outcome data with an AF-free survival rate of 72.83% at the 1-year follow-up in paroxysmal AF patients undergoing cryoballoon ablation. The most frequent, but reversible complication is phrenic nerve palsy with reported incidences up to 10%. All efforts must be taken to overcome this limitation, since the overall major complication rate tends to be lower in cryoballoon compared to radiofrequency ablation. In persistent AF, reported results in cryoballoon ablation had a limited success rate below 50% after a single procedure. A double balloon approach using both cryoballoon sizes might overcome some of the limitations in persistent AF. Prospective data and randomized studies are required. This article outlines the current status of cryoballoon technology in AF ablation therapy.

A continuous-wave optical parametric oscillator around 5-µm wavelength for high-resolution spectroscopy.

We present a continuous-wave optical parametric oscillator (OPO) capable of high resolution spectroscopy at wavelengths between 4.8 µm and 5.4 µm. It is based on periodically poled lithium niobate (PPLN) and is singly resonant for the signal radiation around 1.35 µm. Because of the strong absorption of PPLN at wavelengths longer than 4.5 µm, the OPO threshold rises to the scale of several watts, while it produces idler powers of more than 1 mW and offers continuous tuning over 15 GHz. A supersonic jet spectrometer is used in combination with the OPO to perform measurements of the transient linear molecule Si(2)C(3) at 1968.2 cm(-1). Fifty rovibrational transition frequencies of the ν(3) antisymmetric stretching mode have been determined with an accuracy on the order of 10(-4) cm(-1), and molecular parameters for the ground and the v(3) = 1 state have been determined most precisely.

Hypericum perforatum differentially affects corticosteroid receptor-mRNA expression in human monocytic U-937 cells.

A dysregulation of the hypothalamic-pituitary-adrenocortical (HPA) axis represents a prominent finding in major depression, possibly related to a dysfunction of the corticosteroid receptor system. Antidepressants are involved in the restoration of the altered feed-back mechanism of the HPA-axis, probably via normalization of corticosteroid receptor functions. Since Hypericum perforatum has antidepressive properties, we here examined its putative actions on glucocorticosteroid receptor mRNA levels in human blood cells as a peripheral model for neuroendocrine effects in human brain cells. Our data show that Hypericum (LI 160) affects the cellular mRNA levels of both, the glucocorticoid receptor (GR)-α and its inhibitory counterpart, the GR-ß, at clinically-relevant concentrations. Under these conditions, a bimodal effect was observed. Dose-response studies suggest a rather small effective concentration range and time-effect data show a primary and transient up-regulation of GR-α mRNA levels and a down-regulation of GR-ß mRNA levels after 16 h of treatment. The sodium channel blocker benzamil neutralized the effects of Hypericum, pointing to an at least partial mechanism of action via this pathway. In conclusion, Hypericum treatment differentially affects GR-mRNA levels in the human system. Our data suggest a bimodal effect on GR, resulting in a time-and dose-related modification of GR-mediated cellular effects. Such a mechanism has been alleged as an important way of action for a number of antidepressants. It is the first time that a specific effect on both receptors, especially on the subtype of GR-ß, is shown under antidepressive treatment in a human system under in vitro conditions.

The nu(5) antisymmetric stretching mode of linear C(7) revisited in high resolution.

The nu(5) antisymmetric stretching mode of the linear carbon cluster C(7) has been revisited using a sensitive high-resolution spectrometer, including an external-cavity quantum cascade laser covering the range of interest of 1894-1901 cm(-1). 50 transitions of the nu(5)-band have been recorded and analyzed together with 45 transitions of the nu(4)-band measured by Neubauer-Guenther et al. [J. Chem. Phys. 127, 014313 (2007)]. We determined the band centers, rotational and centrifugal constants very precisely. In addition, 29 hot band transitions have been measured and tentatively assigned to the nu(5)+nu(11)-nu(11) hot band. A global fit of the hot bands nu(5)+nu(11)-nu(11) and nu(4)+nu(11)-nu(11) is presented. Derived l-type doubling constants allow for an experimental estimation of the nu(11)-band center.

Body weight gain induced by atypical antipsychotics: an extension of the monozygotic twin and sib pair study.

BACKGROUND AND OBJECTIVE: In our original study based on five monozygotic twin pairs and seven same-sex sib pairs, we previously showed that genetic factors contribute to body weight gain induced by the atypical antipsychotic clozapine. We aim to study this further by including patients treated with the atypical antipsychotics olanzapine or risperidone as well as opposite-sex sib pairs. METHODS: Twin and sib pairs were identified by a telephone screening. Measured data on weight and other clinical variables were obtained cross-sectionally and retrospectively from medical records. In seven monozygotic twin pairs and 12 sib pairs (total number of patients treated: n = 38, mean age 29.5 +/- 9.5, range 13.7-54.3 years), the similarity in BMI (kg/m(2)) change under these atypical antipsychotics (atypical Delta BMI) and upon additional inclusion of BMI change under prior antipsychotic medication (total Delta BMI) was explored. RESULTS: For total Delta BMI we found greater similarity in antipsychotic-induced BMI change in MZ twin pairs than in sib pairs (intrapair difference) with a heritability of h(2) = 0.6, but not for atypical Delta BMI, possibly because of a genetically influenced weight plateau achieved under antipsychotic medication. CONCLUSION: The results of the present and our previous report suggest a contribution of genetic factors in antipsychotic-induced weight gain of 60-80%.

Impact of drugs approved for treating ADHD on the cell survival and energy metabolism: an in-vitro study in human neuronal and immune cells.

The oxidative and antioxidative properties of psychostimulants such as methylphenidate and amphetamine are discussed controversially. The aim of the present study was to evaluate the impact of psychostimulants and atomoxetine in different concentrations between 31.25 and 5000 ng/ml on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and the impact of psychostimulants and atomoxetine in different concentrations between 500 and 5000 ng/ml on energy metabolism (adenosine triphosphate [ATP] content) in SH-SY5Y cells. Statistical analysis revealed that incubation for 24 h with amphetamine led to a significantly enhanced cell survival in both cell lines after treatment with various (32.5, 125, 250 and 1250 ng/ml) concentrations. Methylphenidate and atomoxetine induced a significantly enhanced cell survival at lower concentrations in the SH-SY5Y cell line, whereas in the U-937 cell line higher concentrations increased the cell survival. Incubation with the highest concentration of methylphenidate (5000 ng/ml) caused a significant reduction of cell survival in both cell types. Measurement of ATP contents in the neuronal cell line revealed no significant effects of the investigated compounds. Our results show that the examined substances exert concentration-dependent effects on cell survival in both applied cell lines.

Effects of antipsychotics and vitamin C on the formation of reactive oxygen species.

There is evidence that reactive oxygen species (ROS) are involved in the pathophysiology of psychiatric disorders such as schizophrenia. Indirect biochemical alterations of ROS formation have been shown for patients treated with antipsychotics as well as for untreated patients. Only one study measured directly the ROS formation after treatment with antipsychotics by using electron spin resonance spectroscopy. The aim of the present examination was to demonstrate the effects of haloperidol, clozapine and olanzapine in concentrations of 18, 90 and 180 µg/mL on the formation of ROS in the whole blood of rats by using electron spin resonance spectroscopy after incubation for 30 min. To test the protective capacity of vitamin C we incubated the highest concentration of each drug with vitamin C (1 mM). Under all treatment conditions, olanzapine led to a significantly higher formation of ROS compared with control conditions, whereas in the cases of haloperidol and clozapine the two higher concentrations induced a significantly enhanced formation of ROS. Vitamin C reduced the ROS production of all drugs tested and for haloperidol and clozapine the level of significance was reached. Our study demonstrated that antipsychotics induce the formation of ROS in the whole blood of rats, which can be reduced by the application of vitamin C.

Effects of quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone on the survival of human neuronal and immune cells in vitro.

Because there are reports on cytotoxic and cytoprotective effects of antipsychotics, the aim of the present study was to evaluate the impacts of different concentrations (1.6-50 microg/mL) of atypical antipsychotics on the survival of human neuronal (neuroblastoma SH-SY5Y) and immune (monocytic U-937) cells and on energy metabolism (ATP level after the incubation with antipsychotics in the concentration of 25 microg/mL). Statistical analysis showed that incubation for 24 h with the antipsychotics quetiapine, risperidone, 9-hydroxyrisperidone and ziprasidone led to a significantly enhanced cell survival in both cell lines in the lower concentrations. Higher concentrations exerted in part cytotoxic effects with the exception of quetiapine, but therapeutically relevant concentrations of the drugs were not cytotoxic in our experiments. Measurement of ATP contents in the neuronal cell line showed significantly increased levels after a 24-h treatment with 25 microg/mL risperidone and 9-hydroxyrisperidone. The other substances produced no effects. Our results show that the antipsychotic substances under investigation exert concentration-dependent effects on cell survival in both cell lines examined.

Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects?

Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003-0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.

Treatment of panic disorder with bupropion in a patient with Parkinson's disease.

We report on a 57-year-old woman, diagnosed with Parkinson's disease, whose panic disorder showed marked improvement after introduction of bupropion, a norepinephrine-dopamine reuptake inhibitor. Additionally a comorbid major depression disappeared under this treatment. Bupropion may be useful for the treatment of patients with both panic disorder and Parkinson's disease.